Finite Element Modeling of Fluid Flow and Heat Transfer in the Weld Pool of CMSX-4 Nickel Based Superalloy

The goal of this study is to determine the characteristics necessary to develop a robust finite element model to accurately predict weld pool shape, size, and fluid properties during a repair weld to a piece of CMSX-4 Nickel-based superalloy. The calculations will take into account the possibilities of turbulence, temperature dependent material property values and different heat input values. It is expected that the model created using the FIDAP software package from FLUENT will be beneficial for future welding simulations. This model was also compared to results from a FORTRAN code written by a separate group at Penn State that have previously been found to be comparable to acceptable experimental values

Placental growth factor (alone or in combination with soluble fms-like tyrosine kinase 1) as an aid to the assessment of women with suspected pre-eclampsia: systematic review and economic analysis

Background: Pre-eclampsia (PE) prediction based on blood pressure, presence of protein in the urine, symptoms and laboratory test abnormalities can result in false-positive diagnoses. This may lead to unnecessary antenatal admissions and preterm delivery. Blood tests that measure placental growth factor (PlGF) or the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to PlGF could aid prediction of PE if either were added to routine clinical assessment or used as a replacement for proteinuria testing.Objectives: To evaluate the diagnostic accuracy and cost-effectiveness of PlGF-based tests for patients referred to secondary care with suspected PE in weeks 20–37 of pregnancy.Design: Systematic reviews and an economic analysis.Data sources: Bibliographic databases including MEDLINE, EMBASE, Web of Science and The Cochrane Library and Database of Abstracts of Reviews of Effects were searched up to July 2015 for English-language references. Conferences, websites, systematic reviews and confidential company submissions were also accessed.Review methods: Systematic reviews of test accuracy and economic studies were conducted to inform an economic analysis. Test accuracy studies were required to include women with suspected PE and report quantitatively the accuracy of PlGF-based tests; their risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. The economic studies review had broad eligibility criteria to capture any types of economic analysis; critical appraisal employed standard checklists consistent with National Institute for Health and Care Excellence criteria. Study selection, critical appraisal and data extraction in both reviews were performed by two reviewers.Economic analysis: An independent economic analysis was conducted based on a decision tree model, using the best evidence available. The model evaluates costs (2014, GBP) from a NHS and Personal Social Services perspective. Given the short analysis time horizon, no discounting was undertaken.Results: Four studies were included in the systematic review of test accuracy: two on Alere’s Triage® PlGF test (Alere, Inc., San Diego, CA, USA) for predicting PE requiring delivery within a specified time and two on Roche Diagnostics’ Elecsys® sFlt-1 to PlGF ratio test (Roche Diagnostics GmbH, Mannheim, Germany) for predicting PE within a specified time. Three studies were included in the systematic review of economic studies, and two confidential company economic analyses were assessed separately. Study heterogeneity precluded meta-analyses of test accuracy or cost-analysis outcomes, so narrative syntheses were conductedto inform the independent economic model. The model predicts that, when supplementing routine clinical assessment for rule-out and rule-in of PE, the two tests would be cost-saving in weeks 20–35 of gestation, and marginally cost-saving in weeks 35–37, but with minuscule impact on quality of life. Length of neonatal intensive care unit stay was the most influential parameter in sensitivity analyses. All othersensitivity analyses had negligible effects on results.Limitations: No head-to-head comparisons of the tests were identified. No studies investigated accuracy of PlGF-based tests when used as a replacement for proteinuria testing. Test accuracy studies were found to be at high risk of clinical review bias.Conclusions: The Triage and Elecsys tests would save money if added to routine clinical assessment for PE. The magnitude of savings is uncertain, but the tests remain cost-saving under worst-case assumptions. Further research is required to clarify how the test results would be interpreted and applied in clinical practice.Study registration: This study is registered as PROSPERO CRD42015017670.Funding: The National Institute for Health Research Health Technology Assessment programme

The prediction of adverse outcomes following major non-cardiac surgery

The prediction of adverse outcomes following major non-cardiac surgery is complex. Clinical variables and risk factors, functional status, electrocardiography and non-invasive cardiac investigations can all be used to assess and stratify the risk of post-operative cardiac morbidity or mortality. Multiple factors can be combined into bed-side scoring systems. Increasingly, cardiac biomarkers such as b-type natriuretic peptide (BNP) have been shown to predict heart failure and mortality in non-surgical populations. In the studies in this thesis, I have investigated the incidence of peri-operative cardiac morbidity and mortality in patients undergoing major non-cardiac surgery and identified clinical variables that predicted adverse outcomes. I have tested the utility of BNP for prediction of cardiac complications. I have investigated the long-term survival of the patients in the cohort to identify predictors of reduced survival. I have examined the predictive value of the pre-operative 12-lead ECG for adverse outcomes. I have also studied the utility of a commonly used risk scoring system, the revised cardiac risk index (RCRI), for prediction of cardiac events. The study was a prospectively performed observational study of consecutive patients undergoing major surgery. The cohort consisted of patients undergoing aortic surgery (25.8%), lower limb bypass surgery (29.8%), amputation (25.2%) and laparotomy (20.0%). The patients underwent post-operative screening for myocardial infarction; consisting of serial ECG and troponin measurement. The end-points were major adverse cardiac event (MACE), defined as myocardial infarction or cardiac death and all-cause mortality. Long term follow-up was performed following discharge. Three hundred and forty-five patients were recruited to the trial. Forty-six patients (13.3%) suffered a peri-operative MACE and twenty-seven patients (7.8%) died in the post-operative period (six weeks). Independent predictors of peri-operative MACE were pre-operative anaemia, urgent surgery, a history of hypertension and age > 70 years. Pre-operative BNP was significantly higher in patients who subsequently went on to have a peri-operative MACE, compared with those who did not. An elevated BNP was an independent predictor of both MACE and peri-operative mortality on multivariate analysis. A low BNP was highly indicative of an uneventful post-operative period, with a negative predictive value of 96% for MACE and 95% for all-cause mortality. Traditional clinical markers of heart disease, such as past history of ischaemic heart disease, prior myocardial infarction, cerebro-vascular disease or history of cardiac failure provided no predictive utility for either MACE or mortality. The mortality rate at 1 year was 19.1%. The median follow-up period was 953 days (IQR 661-1216 days). Age > 70 years, diabetes, hypertension, renal impairment, a history of left ventricular failure, anaemia and urgent surgery were associated with reduced long-term survival. A BNP concentration of 87.5 pg/ml provided the best combined sensitivity and specificity for prediction of long-term mortality. Patients with an elevated BNP (>87.5 pg/ml) had a significantly reduced survival and BNP >87.5 pg/ml independently predicted reduced survival on Cox regression analysis. Urgent surgery and anaemia were also independent predictors of reduced long-term survival. An abnormal ECG was observed in 41% of patients recruited. An abnormal ECG was associated with an increased peri-operative MACE and mortality rate. Ventricular strain and prolonged QTc (>440ms) were ECG abnormalities that predicted MACE on multivariate analysis. Patients with an abnormal ECG, but no prior cardiac history, represent a high risk group that may benefit from optimisation. The studies in this thesis have identified that BNP, a simple pre-operative blood test, provides valuable information regarding the risk of both peri-operative morbidity and mortality, and long-term survival after major non-cardiac surgery. Improved risk stratification could allow targeted intervention and medical optimisation prior to surgery with the aim of modifying the risk of adverse outcomes

Prognostic Factors in Patients with Multiple Recurrences of Well-Differentiated Thyroid Carcinoma

Introduction. Patients with multiple recurrences of well-differentiated thyroid carcinoma (WDTC) have markedly reduced overall survival when compared with those who have ≤1 recurrence of their disease. The purpose of this investigation is to identify prognostic factors for mortality in this subgroup. Methods. Patients with multiple recurrences of WDTC were retrospectively identified from the thyroid cancer database at Mount Sinai Hospital, Toronto (1963–2000). Data on patient, tumor, and recurrence characteristics were collected, and each patient was given a MACIS score. Results. A total of 31 patients were identified (11 male, 20 female; 16–83 years). Using univariate analysis, age >45, stage III/IV disease, distant metastasis, vascular invasion, MACIS score >6, and time to recurrence of <12 months were found to be significant predictors for mortality in this subgroup. Conclusions. Patients with multiple recurrences of WDTC follow a distinct clinical course, marked with multiple treatment failures and a substantial risk of mortality